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Dithiocarbamate derivatives inhibit α-glucosidase through an apparent allosteric site on the enzyme
Chemical Biology & Drug Design ( IF 3.2 ) Pub Date : 2021-05-28 , DOI: 10.1111/cbdd.13897 Usman Ghani 1 , Sajda Ashraf 2 , Zaheer Ul-Haq 2 , Ahmed H Mujamammi 1 , Yusuf Özkay 3 , Fatih Demirci 4, 5 , Zafer Asim Kaplancikli 3
Chemical Biology & Drug Design ( IF 3.2 ) Pub Date : 2021-05-28 , DOI: 10.1111/cbdd.13897 Usman Ghani 1 , Sajda Ashraf 2 , Zaheer Ul-Haq 2 , Ahmed H Mujamammi 1 , Yusuf Özkay 3 , Fatih Demirci 4, 5 , Zafer Asim Kaplancikli 3
Affiliation
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Dithiocarbamate derivatives possess diverse biological activities. This work further expands their activity profile by identifying seven benzylamine-containing dithiocarbamate derivatives with piperazine and piperidine substitutions at the main moiety, and five piperazine-containing dithiocarbamates with various substitutions at the piperazine moiety as new inhibitors of α-glucosidase. Compounds bearing the benzylamine moiety exhibited more potent inhibition of the enzyme than the piperazine derivatives. Majority of the compounds non-competitively inhibited α-glucosidase that led to the identification of a new allosteric site on the enzyme with the help of molecular dynamics and docking studies. These studies suggest that the compounds regulate inhibition of the enzyme by binding to an allosteric site that is located in the vicinity of the active site. This is the first report on the allosteric inhibition of α-glucosidase by dithiocarbamate derivatives that provides insights into the mechanism of inhibition of the enzyme at molecular level. Moreover, it also explores new avenues for drug development of α-glucosidase inhibitors as antidiabetic drugs.
中文翻译：
二硫代氨基甲酸酯衍生物通过酶上明显的变构位点抑制 α-葡萄糖苷酶
二硫代氨基甲酸酯衍生物具有多种生物活性。这项工作通过鉴定七种在主要部分具有哌嗪和哌啶取代的含苄胺的二硫代氨基甲酸酯衍生物和五种在哌嗪部分具有各种取代的含哌嗪二硫代氨基甲酸酯作为新的 α-葡萄糖苷酶抑制剂，进一步扩展了它们的活性谱。带有苄胺部分的化合物对酶的抑制作用比哌嗪衍生物更强。大多数化合物非竞争性抑制 α-葡萄糖苷酶，从而在分子动力学和对接研究的帮助下鉴定了酶上的新变构位点。这些研究表明，这些化合物通过与位于活性位点附近的变构位点结合来调节酶的抑制。这是关于二硫代氨基甲酸酯衍生物对 α-葡萄糖苷酶的变构抑制的第一份报告，它提供了对分子水平上酶抑制机制的见解。此外，它还探索了α-葡萄糖苷酶抑制剂作为抗糖尿病药物的药物开发新途径。
更新日期：2021-07-14
中文翻译：
二硫代氨基甲酸酯衍生物通过酶上明显的变构位点抑制 α-葡萄糖苷酶
二硫代氨基甲酸酯衍生物具有多种生物活性。这项工作通过鉴定七种在主要部分具有哌嗪和哌啶取代的含苄胺的二硫代氨基甲酸酯衍生物和五种在哌嗪部分具有各种取代的含哌嗪二硫代氨基甲酸酯作为新的 α-葡萄糖苷酶抑制剂，进一步扩展了它们的活性谱。带有苄胺部分的化合物对酶的抑制作用比哌嗪衍生物更强。大多数化合物非竞争性抑制 α-葡萄糖苷酶，从而在分子动力学和对接研究的帮助下鉴定了酶上的新变构位点。这些研究表明，这些化合物通过与位于活性位点附近的变构位点结合来调节酶的抑制。这是关于二硫代氨基甲酸酯衍生物对 α-葡萄糖苷酶的变构抑制的第一份报告，它提供了对分子水平上酶抑制机制的见解。此外，它还探索了α-葡萄糖苷酶抑制剂作为抗糖尿病药物的药物开发新途径。
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